A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3
Abstract TL1A (TNFSF15) is a TNF superfamily ligand which can bind the TNFRSF member death receptor 3 (DR3) on T cells and the soluble decoy receptor DcR3. Engagement of DR3 on CD4+ or CD8+ effector T cells by TL1A induces downstream signaling, leading to proliferation and an increase in secretion o...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24984-y |
| _version_ | 1811190444588007424 |
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| author | Adam Zwolak Szeman Ruby Chan Paul Harvilla Sally Mahady Anthony A. Armstrong Leopoldo Luistro Ninkka Tamot Douglas Yamada Mehabaw Derebe Steven Pomerantz Mark Chiu Rajkumar Ganesan Partha Chowdhury |
| author_facet | Adam Zwolak Szeman Ruby Chan Paul Harvilla Sally Mahady Anthony A. Armstrong Leopoldo Luistro Ninkka Tamot Douglas Yamada Mehabaw Derebe Steven Pomerantz Mark Chiu Rajkumar Ganesan Partha Chowdhury |
| author_sort | Adam Zwolak |
| collection | DOAJ |
| description | Abstract TL1A (TNFSF15) is a TNF superfamily ligand which can bind the TNFRSF member death receptor 3 (DR3) on T cells and the soluble decoy receptor DcR3. Engagement of DR3 on CD4+ or CD8+ effector T cells by TL1A induces downstream signaling, leading to proliferation and an increase in secretion of inflammatory cytokines. We designed a stable recombinant TL1A molecule that (1) displays high monodispersity and stability, (2) displays the ability to activate T cells in vitro and in vivo, and (3) lacks binding to DcR3 while retaining functional activity via DR3. Together these results suggest the TL1A ligand can be amenable to therapeutic development on its own or paired with a tumor-targeting moiety. |
| first_indexed | 2024-04-11T14:51:19Z |
| format | Article |
| id | doaj.art-08da83cacee8430d962876b194440306 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T14:51:19Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-08da83cacee8430d962876b1944403062022-12-22T04:17:26ZengNature PortfolioScientific Reports2045-23222022-11-0112111210.1038/s41598-022-24984-yA stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3Adam Zwolak0Szeman Ruby Chan1Paul Harvilla2Sally Mahady3Anthony A. Armstrong4Leopoldo Luistro5Ninkka Tamot6Douglas Yamada7Mehabaw Derebe8Steven Pomerantz9Mark Chiu10Rajkumar Ganesan11Partha Chowdhury12Biologics Discovery, Janssen Research & Development, LLCOncology Discovery, Janssen Research & Development, LLCBiologics Discovery, Janssen Research & Development, LLCOncology Discovery, Janssen Research & Development, LLCBiologics Discovery, Janssen Research & Development, LLCOncology Discovery, Janssen Research & Development, LLCBiologics Discovery, Janssen Research & Development, LLCOncology Discovery, Janssen Research & Development, LLCMerck Research Laboratories, Discovery Biologics, Protein SciencesBiologics Discovery, Janssen Research & Development, LLCTavotek BiotherapeuticsImmunotherapeutics, AmgenCell Engineering and Early Development, Janssen Research & DevelopmentAbstract TL1A (TNFSF15) is a TNF superfamily ligand which can bind the TNFRSF member death receptor 3 (DR3) on T cells and the soluble decoy receptor DcR3. Engagement of DR3 on CD4+ or CD8+ effector T cells by TL1A induces downstream signaling, leading to proliferation and an increase in secretion of inflammatory cytokines. We designed a stable recombinant TL1A molecule that (1) displays high monodispersity and stability, (2) displays the ability to activate T cells in vitro and in vivo, and (3) lacks binding to DcR3 while retaining functional activity via DR3. Together these results suggest the TL1A ligand can be amenable to therapeutic development on its own or paired with a tumor-targeting moiety.https://doi.org/10.1038/s41598-022-24984-y |
| spellingShingle | Adam Zwolak Szeman Ruby Chan Paul Harvilla Sally Mahady Anthony A. Armstrong Leopoldo Luistro Ninkka Tamot Douglas Yamada Mehabaw Derebe Steven Pomerantz Mark Chiu Rajkumar Ganesan Partha Chowdhury A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3 Scientific Reports |
| title | A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3 |
| title_full | A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3 |
| title_fullStr | A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3 |
| title_full_unstemmed | A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3 |
| title_short | A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3 |
| title_sort | stable engineered tl1a ligand co stimulates t cells via specific binding to dr3 |
| url | https://doi.org/10.1038/s41598-022-24984-y |
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